Significance Intrauterine growth restriction (IUGR) is a significant pediatric problem and a major cause of perinatal morbidity and mortality. In order to prevent and/or correct IUGR before irreversible damage is done, specific mechanisms/interactions which regulate fetal growth must be known. Insulin-like growth factor (IGF) has clearly been shown to be a key modulator of somatic fetal growth, and has also been shown to also regulate vascular tone which is proposed to be mediated through nitric oxide (NO) production. Objectives A monkey model of IUGR induced by the chronic maternal administration of a NO synthase inhibitor (NG-nitro-L-arginine methyl ester; L-NAME) is used to evaluate the relationship between the IGF and NO axes in the induction of IUGR. Results L-NAME was shown to induce IUGR when administered during the late second and third trimesters, with a direct effect on the fetal IGF-I:IGF binding protein (IGFBP-3) ratio (reduced levels of IGF-I, elevation in IGFBP-3). Maternal and fetal NO levels were found to be within normal limits suggesting a compensatory rise in NO via inducible NO synthase (iNOS). These data imply that the control of NO production may involve IGF-I expression, and the manner and degree in which NO is synthesized may determine whether NO production has a beneficial (vasodilation) or detrimental (cytotoxicity and IUGR) effect. Future Directions Studies will explore the role and relationship of IGF and iNOS gene expression and apoptosis in IUGR, and supplemental fetal IGF-I administration in negating the fetal catabolic and growth-restricting effects induced by NO synthase inhibition. KEYWORDS fetal growth restriction, nitric oxide, IGF-I, iNOS